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Dose-escalation was finished, but no clear correlation between fluorescence and tumor grade was established
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For locally advanced esophageal cancer (EC), neoadjuvant chemoradiotherapy (nCRT) for 5 weeks followed by esophagectomy and lymphadenectomy, if necessary, is standard of care. It is reported that the pathological complete response (pCR) rate after nCRT ranges from 16% to 43%, with a median of 26.5%. According to current clinical guidelines, patients who achieved pCR still go for surgery even though those patients who achieved pCR may not benefit from surgery. Besides, about 50% of EC patients may have post-operative complications including pneumonia, anastomotic leakage, recurrent laryngeal nerve paralysis, which lead to low health-related quality of life (HQoL).
The golden standard to test the pathological response is by pathological assessment of the surgical specimen and thus after surgery. Theoretically, if pCR after nCRT can be predicted accurately before surgery by advanced imaging techniques, patients could have a wait-and-see. The wait-and-see procedure includes regular follow-up and salvage surgery if recurrence is present. Therefore, molecular fluorescence endoscopy (FME) using near-infrared fluorescence (NIRF) tracer bevacizumab-800CW targeting vascular endothelial growth factor combined with high-definition white light (HD-WL) endoscopy is expected to be a promising technique to monitor pCR and fill the gap.
See brief summary
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| NIR endoscopy with 4.5 mg bevacizumab-800CW | Experimental | A non-randomized, non-blinded, prospective, feasibility study.
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| NIR endoscopy with 10 mg bevacizumab-800CW | Experimental | A non-randomized, non-blinded, prospective, feasibility study.
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| NIR endoscopy with 25 mg bevacizumab-800CW | Experimental | A non-randomized, non-blinded, prospective, feasibility study.
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Bevacizumab-IRDye800CW | Drug | Intravenous administration of 4.5, 10 or 25 mg of Bevacizumab-IRDye800CW prior to the endoscopic procedure |
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| Measure | Description | Time Frame |
|---|---|---|
| Discrimination of tumorous and non-tumorous tissue based on in vivo and ex vivo fluorescence measurements from bevacizumab-800CW gained during fluorescence endoscopy procedure | To determine the sensitivity of the marker bevacizumab-800CW in discriminating between tumorous and non-tumorous tissue prior to and post neoadjuvant chemoradiotherapy, to identify patients who benefit from the chemoradiotherapy. | Three days after tracer injection |
| Safety of bevacizumab-800CW administration by monitoring vital signs and/or (serious) adverse events. | Monitoring vital signs (blood pressure, heart frequency and temperature) and/or (serious) adverse events that are related to the administration of bevacizumab-800CW | Up to 14 days after tracer injection |
| Measure | Description | Time Frame |
|---|---|---|
| The correlation of in vivo and ex vivo fluorescent signals to histopathological analysis results | Correlate the H/E images to the fluorescent images made with multiple ex vivo imaging modalities. | Up to 1,5 year |
| Quantification of the fluorescent signal by MDSFR/SFF spectroscopy |
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Inclusion Criteria:
Exclusion Criteria:
Patients with psychological diseases or medical issues who are not able to sign informed consent form;
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| Name | Affiliation | Role |
|---|---|---|
| W. B. Nagengast, MD, PhD, PharmD | University Medical Center Groningen | Principal Investigator |
| G. M. van Dam, MD, PhD | University Medical Center Groningen | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Medical Center Groningen | Groningen | 9713 GZ | Netherlands |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25364580 | Background | Duan XF, Tang P, Yu ZT. Neoadjuvant chemoradiotherapy for resectable esophageal cancer: an in-depth study of randomized controlled trials and literature review. Cancer Biol Med. 2014 Sep;11(3):191-201. doi: 10.7497/j.issn.2095-3941.2014.03.005. | |
| 26287423 | Background | Booka E, Takeuchi H, Nishi T, Matsuda S, Kaburagi T, Fukuda K, Nakamura R, Takahashi T, Wada N, Kawakubo H, Omori T, Kitagawa Y. The Impact of Postoperative Complications on Survivals After Esophagectomy for Esophageal Cancer. Medicine (Baltimore). 2015 Aug;94(33):e1369. doi: 10.1097/MD.0000000000001369. |
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| ID | Term |
|---|---|
| D004938 | Esophageal Neoplasms |
| ID | Term |
|---|---|
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
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| Molecular Fluorescence Endoscopy platform | Device | A flexible fluorescence fiber-bundle is attached to a fluorescence camera platform to enable the detection of fluorescence signals. The fluorescence fiber-probe is inserted through the standard working channel of the standard clinical endoscope. Fluorescence imaging will be performed prior to and post the chemoradiotherapy. |
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Multi-diameter single-fiber reflectance with single-fiber fluorescence (MDSFR/SFF) spectroscopy can measure the fluorescence signal quantitatively, both in vivo and ex vivo. |
| Up to 1,5 year |
| To localization and distribution of bevacizumab-800CW fluorescent signal at cell level observed in vivo by confocal laser endomicroscopy (CLE) | CLE is a confocal laser endomicroscopy system which enables in vivo microscopic images of the tissue | Up to 1,5 year |
| Assessment of the (sub)-cellular distribution of bevacizumab-800CW by ex vivo fluorescence microscopy | Imaging of the distribution of bevacizumab-800CW with a fluorescence microscoop. | Up to 1,5 year |
| The variation in fluorescence intensity between fluorescence molecular endoscopy before and after neoadjuvant chemoradiotherapy defined as the tumor to background ratio and intrinsic fluorescence. | Both the images and specific measurements are used to calculate the fluorescence intensity (TBR & intrinsic fluorescence) and a difference between the before and after intensity is calculated. | Up to 1,5 year |
| 23026283 | Background | Raymond D. Complications of esophagectomy. Surg Clin North Am. 2012 Oct;92(5):1299-313. doi: 10.1016/j.suc.2012.07.007. |
| D006258 |
| Head and Neck Neoplasms |
| D004066 | Digestive System Diseases |
| D004935 | Esophageal Diseases |
| D005767 | Gastrointestinal Diseases |